Insertion and removal methods and apparatus for therapeutic devices

ABSTRACT

Described herein is an apparatus to insert an implantable therapeutic device into a patient. The apparatus includes a proximal handle ( 210 ) and a distal placement portion ( 220 ) coupled to the proximal handle and configured to hold the implantable therapeutic device. The distal placement portion includes a first side ( 222 ) having a first engagement structure ( 251 ) at a distal end of the first side, the first engagement structure configured to surround at least a first portion of a proximal end region of the implantable therapeutic device. The distal placement portion includes a second, opposite side ( 224 ) having a second engagement structure ( 253 ) at a distal end of the second side, the second engagement structure configured to surround at least a second, opposite portion of the proximal end region of the implantable therapeutic device.

CROSS-REFERENCE TO RELATED APPLICATIONS

The current application claims priority under 35 U.S.C. §199(e) to U.S.Provisional Patent Application No. 61/594,961 filed on Feb. 3, 2012, thedisclosure of which is incorporated herein by reference in its entirety.

BACKGROUND

The present disclosure is generally related to methods and apparatus toinsert and remove implantable devices. Although specific reference ismade to placement in the eye, embodiments as described herein can beused with many implantable devices in locations away from the eye, suchas orthopedic, intraluminal and transdermal locations.

Implantable devices can be used to provide a therapeutic agent to one ormore locations of a patient. The implantable device may have a reservoirof therapeutic agent, and a structure to retain the implantable deviceat a desired location of the patient. The implantable device may have achamber for storing the therapeutic agent, and the agent can be releasedinto the patient to provide a therapeutic benefit. After an amount oftime, the amount of fluid released can be less than ideal, and the fluidof the implantable device may be replaced, refilled, or exchanged toprovide additional amounts of therapeutic agent to extend the therapy.

The prior methods and apparatus to place an implantable device in thebody can be less than ideal in at least some instances. For example, theamount of therapeutic fluid placed in an implanted therapeutic devicewith injection can be less than ideal in at least some instances. Atleast some of the prior devices implanted in the eye can be small todecrease interference with vision, and the refill port of such devicescan be difficult to fill in at least some instances. The eye can move,and alignment and placement of the implantable device in the eye can bemore difficult than would be ideal in at least some instances.

In light of the above, it would be desirable to provide improvedtreatments for the eye and improved methods and apparatus to placeimplantable devices in the eye and to place therapeutic fluids in theimplantable devices. Ideally, these treatments, methods and apparatuswould decrease at least some of the deficiencies of the prior methodsand apparatus, and would provide improved placement and removal ofdevices implanted within the eye.

SUMMARY

Embodiments of the present disclosure provide improved methods andapparatus to insert and remove an implantable device to treat a patient.In many embodiments, the methods and apparatus can provide injection ofa therapeutic agent into an implantable device prior to insertion. Theimplantable device can be manufactured and provided to a clinic withouta therapeutic agent, such that the therapeutic agent can be placed inthe implantable device in the clinic prior to insertion.

In a first aspect, described herein is an apparatus to insert animplantable therapeutic device into a patient. The apparatus includes aproximal handle, and a distal placement portion coupled to the proximalhandle and configured to hold the implantable therapeutic device. Thedistal placement portion includes a first side having a first engagementstructure at a distal end of the first side, the first engagementstructure configured to surround at least a first portion of a proximalend region of the implantable therapeutic device. The distal placementportion includes a second, opposite side having a second engagementstructure at a distal end of the second side, the second engagementstructure configured to surround at least a second, opposite portion ofthe proximal end region of the implantable therapeutic device.

The apparatus can further include the implantable therapeutic device.The implantable therapeutic device can include a retention structure atthe proximal end region having a narrow portion, a shoulder and aproximal extension. Each of the first and second engagement structurescan include a protrusion having a surface contour shaped and sized toengage a portion of the retention structure. Each of the protrusions canbe configured to extend into the narrow portion. The protrusions canextend into the narrow portion, a proximal surface of each protrusioncan engage a distal surface of the proximal extension and a distalsurface of each protrusion can engage the shoulder.

The distal placement portion can further include a recess through whicha proximal surface of the proximal extension is accessible. The distalplacement portion can further include a guide having at least one guidesurface configured to support and maintain alignment of a needleextending at an angle oblique to a longitudinal axis of the implantabledevice prior to penetration of the implantable device by the needle. Theneedle can include a connector and wherein the at least one guidesurface has a shape complimentary to the connector to receive theconnector and maintain alignment of the needle relative to theimplantable device. The proximal handle can include first and secondopposing handles extending on opposite sides of a longitudinal axis. Thefirst opposing handle can be coupled to a proximal end of the first sideand the second opposing handle can be coupled to a proximal end of thesecond side. The first and second opposing handles can be configured tourge the first side and the second side toward each other to engage theimplantable device when the first and second opposing handles move awayfrom the axis and to urge the first side and the second side away fromeach other to release the implantable device when the first and secondopposing handles move toward the axis. The first and second opposinghandles can be configured to urge the first side and the second sidetoward each other to engage the implantable device when the first andsecond opposing handles move toward the axis and to urge the first sideand the second side away from each other to release the implantabledevice when the first and second opposing handles move away from theaxis.

In an interrelated aspect, disclosed herein is a method of treating apatient including holding with an insertion apparatus an implantabledevice having an axis and a penetrable barrier, such that the axis ofthe implantable device and an axis of the insertion apparatus areconcentric. The method includes advancing a needle through thepenetrable barrier at an angle oblique to the concentric axes. Themethod includes injecting a therapeutic fluid through the needleadvanced through the penetrable barrier and into a reservoir chamber ofthe implantable device. The method includes implanting the implantabledevice into an incision in a tissue of the patient.

The axis of the implantable device and the axis of the insertionapparatus can be concentric when the therapeutic fluid is injected intothe reservoir chamber of the implantable device.

In an interrelated aspect disclosed herein is a kit to treat a patientincluding an insertion apparatus of any of those described herein, animplantable therapeutic device, and packaging to contain the insertionapparatus and the implantable therapeutic device.

Additional aspects are recited in the claims below, and can provideadditional summary in accordance with embodiments as described herein.It is contemplated that the embodiments as described herein and recitedin the claims may be combined in many ways, and any one or more of theelements recited in the claims can be combined together in accordancewith embodiments and teachings as described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows an eye suitable for incorporation of the therapeuticdevice, in accordance with embodiments;

FIG. 1B shows a therapeutic device implanted under the conjunctiva andextending through the sclera to release a therapeutic agent intovitreous humor of the eye so as to treat the retina of the eye, inaccordance with embodiments;

FIG. 1C-1 shows a side cross-sectional view of a therapeutic deviceincluding a retention structure having a cross-section sized to fit inan elongate incision, in accordance with embodiments;

FIG. 1C-2 shows an isometric view of the therapeutic device as in FIG.1C-1;

FIG. 1C-3 shows a top view of the therapeutic device as in FIG. 1C-1;

FIG. 1C-4 shows a side cross sectional view along the short side of theretention structure of the therapeutic device as in FIG. 1C-1;

FIG. 1C-5 shows a side view of the therapeutic device as in FIG. 1C-1implanted in the sclera;

FIG. 1C-6 shows a cutting tool including a blade having a widthcorresponding to the perimeter of the barrier and the perimeter of thenarrow retention structure portion, in accordance with embodiments;

FIG. 2A shows an isometric view of the therapeutic device having aretention structure with an elongate cross-sectional size, in accordancewith embodiments;

FIG. 2B shows a distal end view of the therapeutic device as in FIG. 2A;

FIG. 2C1 shows a side view of the short axis of the narrow neck portionof the therapeutic device as in FIG. 2A;

FIG. 2C2 shows a side view of the long axis of the narrow neck portionof the therapeutic device as in FIG. 2A;

FIG. 2D shows a proximal view of the therapeutic device as in FIGS. 2A;

FIGS. 2E to 2G show exploded assembly drawings for the therapeuticdevice as in FIGS. 2A to 2D;

FIG. 3A shows an insertion apparatus in accordance with embodiments;

FIGS. 3B and 3C show front and back views, respectively, of a distalplacement portion of the insertion apparatus of FIG. 3A;

FIGS. 3D and 3E show front and back views, respectively, of the distalplacement portion of the insertion apparatus engaging the implantabledevice;

FIG. 3F shows an injector having a needle advanced toward theimplantable device held with the insertion apparatus, in accordance withembodiments;

FIG. 3G shows a side view of the implantable device held with one of theengagement structures and the needle aligned obliquely with the axis ofthe implantable device, in accordance with embodiments;

FIG. 3H shows the needle inserted obliquely into the implantable deviceto inject the therapeutic agent, in accordance with embodiments;

FIG. 4A shows a removal tool, in accordance with embodiments;

FIG. 4B shows the removal tool of FIG. 4A aligned with an implantabledevice, in accordance with embodiments;

FIGS. 4C and 4D show top and bottom views, respectively, of the removaltool of FIGS. 4A and 4B holding the implantable device, in accordancewith embodiments;

FIG. 4E shows the removal tool having opposing components, in accordancewith embodiments;

FIG. 5A shows a needle inserted into an air-filled implantable device,in accordance with embodiments;

FIG. 5B shows a therapeutic fluid placed in the implantable device ofFIG. 5A, in accordance with embodiments;

FIG. 5C shows the therapeutic fluid injected into an implantable deviceand seeping through a porous structure on the distal end of the deviceof FIG. 5A, in accordance with embodiments;

FIG. 5D shows the implantable device being placed in the eye, inaccordance with embodiments;

FIG. 6A shows a kit having an insertion apparatus, in accordance withembodiments;

FIG. 6B shows a kit having a removal tool, in accordance withembodiments;

DETAILED DESCRIPTION

Embodiments as described herein can be combined in many ways to treatone or more diseases of a patient such as a disease of the eye. Theembodiments as described herein are well suited to treat patients with atherapeutic agent for an extended time, such as may be provided with animplantable device. Although specific reference is made to ophthalmictreatment of the eye, the methods and apparatus to place and remove animplantable device can be used with many implantable devices andtreatments of one or more of many diseases, such as systemic medicationto treat systemic disease, orthopedic treatment to treat orthopedicdisorders, or dental treatment, for example. The insertion and removalapparatus and methods as described herein are well suited for use withmany drug delivery devices, such as refillable diffusion based devices,and can be exceptionally well suited for diffusion devices having aporous drug release structure configured for extended release in whichthe porous structure inhibits flow of fluid during exchange. Theinsertion and removal apparatus and methods as describe herein are wellsuited for diagnoses and treatment of the eye, for example withdiagnosis and treatment of the eye based on the implantable device fluidreceived with the exchange apparatus with the fluid is injected. Themethods and apparatus as described herein are well suited forcombination with implantable devices and injector apparatus as describedin U.S. patent application Ser. No. 12/696,678, filed on Jan. 29, 2010,entitled “Posterior Segment Drug Delivery”, Publication No.2010/0255061; and U.S. PCT Pat. App. No. PCT/US2011/046812, filed Aug.5, 2011, entitled “Injector Apparatus and Method for Drug Delivery”, theentire disclosures of which are incorporated herein by reference.

As used herein like numerals and/or letters denote like elements in thedrawings and text as will be apparent to a person of ordinary skill inthe art.

FIG. 1A shows an eye 10 suitable for placement of the therapeuticdevice. The eye has a cornea 12 and a lens 22 configured to form animage on the retina 26. The cornea can extend to a limbus 14 of the eye,and the limbus can connect to a sclera 24 of the eye. A conjunctiva 16of the eye can be disposed over the sclera 24. The lens 22 canaccommodate to focus on an object seen by the patient. The eye has aniris 18 that may expand and contract in response to light. The eye alsoincludes a choroid 28 disposed the between the sclera 24 and the retina26. The retina includes the macula 32. The eye includes a pars plana 20,which is an example of a region of the eye suitable for placement andretention, for example anchoring, of the therapeutic device 100 asdescribed herein and shown in 1B. The pars plana region 20 may includesclera 24 and conjunctiva 16 disposed between the retina 26 and cornea12. The therapeutic device can be positioned so as to extend from thepars plana region 20 into the vitreous humor 30 to release thetherapeutic agent. The therapeutic agent can be released into thevitreous humor 30, such that the therapeutic agent arrives at the retina26 and choroids 28 for therapeutic effect on the macula 32. The vitreoushumor of the eye 30 includes a liquid disposed between the lens 22 andthe retina 26. The vitreous humor 30 may include convection currents todeliver the therapeutic agent to the macula 32.

FIG. 1B shows a therapeutic device 100 implanted under the conjunctiva16 and extending through the sclera 24 to release a therapeutic agent110 into vitreous humor 30 of the eye 10 so as to treat the retina 26 ofthe eye. The therapeutic device 100 can include a retention structure120 such as a smooth protrusion configured for placement along thesclera 24 and under the conjunctiva 16, such that the conjunctiva 16 cancover the therapeutic device and protect the therapeutic device 100.When the therapeutic agent 110 is inserted into the device 100, theconjunctiva 16 may be lifted away, incised, or punctured with a needleto access the therapeutic device 100. The eye 10 can include aninsertion of the tendon 27 of the superior rectus muscle to couple thesclera 24 of the eye to the superior rectus muscle. The device 100 maybe positioned in many locations of the pars plana region 20, for exampleaway from tendon 27 and one or more of posterior to the tendon,posterior to the tendon, under the tendon, or with nasal or temporalplacement of the therapeutic device.

While the implant can be positioned in the eye in many ways, work inrelation to embodiments suggests that placement in the pars plana regioncan release therapeutic agent into the vitreous to treat the retina, forexample therapeutic agent including an active ingredient composed oflarge molecules.

Therapeutic agents 110 suitable for use with device 100 include one ormore of many therapeutic agents, for example as listed in Table 1A,herein below. The therapeutic agent 110 of device 100 can include one ormore of an active ingredient of the therapeutic agent, a formulation ofthe therapeutic agent, a commercially available formulation of thetherapeutic agent, a physician prepared formulation of therapeuticagent, a pharmacist prepared formulation of the therapeutic agent, or acommercially available formulation of therapeutic agent having anexcipient. The therapeutic agent may be referred to with generic name ora trade name, for example as shown in Table 1A.

The therapeutic device 100 can be implanted in the eye to treat the eyefor as long as is helpful and beneficial to the patient. For example thedevice can be implanted for at least about 5 years, such as permanentlyfor the life of the patient. Alternatively or in combination, the devicecan be removed when no longer helpful or beneficial for treatment of thepatient.

FIG. 1C-1 shows a side cross-sectional view of therapeutic device 100including a retention structure 120 having a cross-section sized to fitin an elongate incision. The cross-section sized to fit in the elongateincision can include a narrow portion 120N of retention structure 120that is sized smaller than the extension 122. The narrow portion 120N(shown in FIG. 1C-2) sized to fit in the elongate incision can includean elongate cross section 120NE sized to fit in the incision. The narrowportion 120N can include a cross-section having a first cross-sectionallong distance 120NL, or first dimensional width, and a secondcross-sectional short distance 120NS (shown in FIG. 1C-2), or seconddimensional width, in which the first cross-sectional distance across isgreater than the second cross-sectional distance across such that thenarrow portion 120N includes an elongate cross-sectional profile. Thefirst cross-sectional long distance 120NL may extend along a first axis120N1 and the second cross-sectional short distance 120NS may extendalong a second axis 120N2 (shown in FIG. 1C-2).

In many embodiments, the retention structure 120 includes a shoulder120S extending from the narrow portion 120N to the wall of the reservoirchamber 140, which can include a rigid or expandable annular wall. Theshoulder portion 120S can extend from the narrow portion so as to engagethe sclera opposite extension 122 and hold the device 100 in the parsplana region. The shoulder 120S of retention structure 120 can include afirst shoulder 120S1 on a first side of the retention structure and asecond shoulder 120S2 on a second side of the retention structure withaxis 120N1 extending therebetween (as shown in 1C-5). Alternatively, theretention structure 120 can include a rotationally symmetric narrowportion 120N having a first side and a second side to fit a dilatedincision of the eye, for example, and shoulder 120S can include arotationally symmetric shoulder extending from the narrow portion 120Nto engage a lower portion of the sclera.

The elongate cross section 120NE, shown in FIGS. 1C-2 and 1C-3, of thenarrow portion 120N can be sized in many ways to fit the incision. Theelongate cross section 120NE having long distance 120NL and shortdistance 120NS and can include one or more of many shapes such asdilated slit, dilated slot, lentoid, oval, ovoid, or elliptical. Thedilated slit shape and dilated slot shape may correspond to the shapesclera tissue assumes when cut and dilated. The lentoid shape maycorrespond to a biconvex lens shape. The elongate cross-section of thenarrow portion can include a first curve along a first axis and a secondcurve along a second axis different than the first curve.

The porous structure 150 can be located on a distal end portion of thetherapeutic device, and the retention structure 120 can be located on aproximal portion of therapeutic device 100, as shown in FIGS. 1C-1,1C-2, 1C-4, and 1C-5. The porous structure 150 can include one or moreof many porous structures such as a sintered material, openings in anon-permeable material, openings having a size and number to releasetherapeutic agent at an intended rate, a plurality of holes etched in amaterial, a semi-permeable membrane, or nano-channels, for example.

The reservoir 130 can be configured in many ways, and can include arigid walled reservoir, for example, or an expandable reservoir. Thebarrier 160 may define a size of reservoir 130. The barrier 160 andreservoir 130 may each include a circular, an elliptical, oval or othercross-sectional size, for example.

FIG. 1C-2 shows an isometric view of the therapeutic device as in FIG.1C-1.

FIG. 1C-3 shows a top view of the therapeutic device as in FIG. 1C-1.

FIG. 1C-4 shows a side cross sectional view along the short side of theretention structure of the therapeutic device as in FIG. 1C-1.

FIG. 1C-5 shows a side view of the therapeutic device as in FIG. 1C-1implanted in the sclera.

FIG. 1C-6 shows a cutting tool 710 including a blade 714 having a width712 corresponding to perimeter 160P (shown in FIGS. 1C-1, 1C-2, and1C-3) of the barrier 160 and the perimeter 120NP of the narrow portion.The cutting tool can be sized to the narrow portion 120N so as to sealsubstantially the incision with the narrow portion when the narrowportion is positioned against the sclera. For example, the width 712 canbe about one half of the perimeter 160P of the barrier 160 and about onehalf of the perimeter 120NP of the narrow portion 120N. For example, theoutside diameter of the tube of barrier 160 can be about 3 mm such thatthe perimeter of 160P is about 6 mm, and the narrow portion perimeter120NP is about 6 mm. The width 712 of the blade 710 can be about 3 mmsuch that the incision includes an opening having a perimeter of about 6mm so as to seal the incision with the narrow portion 120N.Alternatively, perimeter 160P of barrier 160 may have a size slightlylarger than the incision and the perimeter of the narrow portion.

The retention structure includes narrow portion 120N having shortdistance 120NS and long distance 120NL so as to fit in an elongateincision along the pars plana of the eye. The retention structureincludes extension 122, and the extension 122 of the retention structure120 can include a short distance across 122S and a long distance across122L, aligned with the short distance 120NS and long distance 120NL ofthe narrow portion 120N of the retention structure 120. The narrowportion 120 can include an indentation 120I sized to receive the sclera,and the indention 120I can include an indentation relative to a maximumdimension across the reservoir chamber 140 and the extension 122 suchthat the sclera is retained with the indentation 120I. The indentation120I can include a portion of the extension 122, a portion of theshoulder 120S and a portion of the retention structure extendingtherebetween, for example.

The therapeutic device 100 can include a non-circular cross-sectionalsize, and the reservoir chamber 140 can include a rigid walled reservoirhaving a non-circular, for example elliptical or lentoid cross-sectionalsize.

FIG. 2A shows an isometric view of the therapeutic device having aretention structure including a narrow portion 120N with an elongatecross-sectional size 120NE.

FIG. 2B shows a distal end view of the therapeutic device as in FIG. 2A.

FIG. 2C1 shows a side view of the short distance 120NS of the narrowportion 120N of the therapeutic device as in FIG. 2A.

FIG. 2C2 shows a side view of the long distance 120NL of the narrowportion 120N of the therapeutic device 100 as in FIG. 2A.

FIG. 2D shows a proximal view of the therapeutic device as in FIG. 2A.

FIGS. 2E to 2G show exploded assembly drawings for the therapeuticdevice 100 as in FIGS. 2A to 2D. The assembly drawings show isometricand thin side profiles views of the elongate portion 120NE of the narrowportion of the retention structure 120N. The therapeutic device 100 hasan elongate axis 100A.

The penetrable barrier 184, for example the septum, can be inserted intothe access port 180. The penetrable barrier can include an elasticmaterial sized such that the penetrable barrier can be inserted into theaccess port 180. The implantable device can include penetrable barrier184 having a first outer and a second inner surface and a thicknessextending a distance 184D between the first surface and the secondsurface. The penetrable barrier can include one or more elasticmaterials such as siloxane or rubber. The penetrable barrier can includetabs 184T to retain the penetrable barrier in the access port. Thepenetrable barrier 184 can include a beveled upper rim 184R sized toseal the access port 180. The access port 180 of the reservoir container130 can include a beveled upper surface to engage the beveled rim andseal the penetrable barrier against the access port 180 when the tabs184T engage an inner annular or elongate channel of the access port. Thepenetrable barrier 184 can include an opaque material, for example agrey material, for example silicone, such that the penetrable barriercan be visualized by the patient and treating physician.

The reservoir container 130 of the device can include a rigidbiocompatible material that extends at least from the retentionstructure to the rigid porous structure, such that the reservoirincludes a substantially constant volume when the therapeutic agent isreleased with the rigid porous structure so as to maintain a stablerelease rate profile, for example when the patient moves. Alternativelyor in combination, the reservoir container 130 can include an opticallytransmissive material such that the reservoir container 130 can betranslucent, for example transparent, such that the chamber of reservoir140 can be visualized when the device is loaded with therapeutic agentoutside the patient prior to implantation, for example when injectedwith a formulation of therapeutic agent prior to implantation in thephysician's office. This visualization of the reservoir 140 can behelpful to ensure that the reservoir 140 is properly filled withtherapeutic agent by the treating physician or assistant prior toimplantation. The reservoir container can include one or more of manybiocompatible materials such as acrylates, polymethylmethacrylate,siloxanes, metals, titanium stainless steel, polycarbonate,polyetheretherketone (PEEK), polyethylene, polyethylene terephthalate(PET), polyimide, polyamide-imide, polypropylene, polysulfone,polyurethane, polyvinylidene fluoride or PTFE. The biocompatiblematerial of the reservoir container can include an opticallytransmissive material such as one or more of acrylate, polyacrylate,methlymethacraylate, polymethlymethacrylate (PMMA), polyacarbonate orsiloxane. The reservoir container 130 can be machined from a piece ofmaterial, or injection molded, so as to form the retention structure 120including extension 122 and the elongate narrow portion 120NE. Theextension 122 can include a translucent material such that the physiciancan visualize tissue under the flange to assess the patient and todecrease appearance of the device 100 when implanted. The reservoircontainer 130 can include a channel extending along axis 100A from theaccess port 180 to porous structure 150, such that formulation injectedinto device 100 can be released in accordance with the volume of thereservoir and release rate of the porous structure 150 as describedherein. The porous structure 150 can be affixed to the distal end oftherapeutic device 100, for example with glue. Alternatively or incombination, the distal end of the reservoir container 130 can includean inner diameter sized to receive the porous structure 150, and thereservoir container 130 can include a stop to position the porousstructure 150 at a predetermined location on the distal end so as todefine a predetermined size of reservoir 140.

FIG. 3A shows an insertion apparatus 200. The insertion apparatusincludes a proximal handle 210 and a distal placement portion 220. Thehandle 210 includes a first extension 212 and a second extension 214. Aproximal end portion 216 couples the first extension 212 to the secondextension 214. The insertion apparatus 200 includes an axis 200Aextending along an elongate dimension of the insertion apparatus 200.

The proximal handle 210 includes structures to manipulate the distalplacement portion 220. The first extension 212 and second extension 214may be combined in many ways to manipulate the distal placement portion220. The first extension 212 and the second extension 214 may extend toopposing sides of the distal portion 220. The first extension 212 andthe second extension 214 and can include a resilient spring having theextensions coupled together at the distal end portion 216, for examplewith a weld on the distal end portion 216. The user can urge the firstextension 212 toward the second extension 214 against the resilientextensions as shown with arrows 218, and the user can release theextensions, such that the spring forces urges the first extension 212away from the second extension 214 opposite arrows 218.

The distal placement portion 220 includes structures to hold and placethe implantable device 100. The distal placement portion 220 includes aguide 230 and an engagement structure 250. The engagement structure 250is configured to engage the implantable device 100, and the guide 230 isconfigured to facilitate alignment and access to the implantable device100 with a needle or other filling device so as to place therapeuticagent inside the implantable device 100. The guide 230 can be located ona front 240 of the placement portion 220, and can be readily viewed by auser. The front 240 is located opposite a back 242. The guide 230located on the front 240 allows viewing of the recess 231 when theneedle is advanced into the recess, as will be described in more detailbelow. The distal placement portion 220 includes a first side 222 and asecond side 224 located opposite the first side 222. The first side 222is movable opposite the second side 224 so as to engage the implantabledevice 100 with the first side 222 and the second side 224.

The engagement structure 250 can be configured to contact theimplantable device in many ways, and can include a first engagementstructure 251 on first side 222 and a second engagement structure 253 onthe second side 224 opposite the first engagement structure. The firstengagement structure 251 on first side 222 includes a first projection252 extending at least partially around axis 200A. The second engagementstructure 252 on second side 224 includes a second projection 254extending at least partially around axis 200A opposite the firstprojection 252. The first and second projections 252, 254 may extendcircumferentially and axially in relation to axis 100.

The guide 230 of the distal placement portion 220 can be configured inmany ways to guide a needle toward recess 231 when the insertionapparatus holds the implantable device with the engagement structure250. The guide 230 can include the first side 222 and the second side224. The guide 230 can include a plurality of recessed surfaces thatallow a short needle to be used to place the therapeutic fluid includingtherapeutic agent 110 in the implantable device. The guide 230 caninclude a first proximal guide surface 232 and first intermediate guidesurface 233, and a first distal guide surface 236 on the first side 222.The guide 230 can include a second proximal guide surface 234 and secondintermediate guide surface 235, and a second distal guide surface 238 onthe second side 224. The guide surfaces are arranged to provide a visualreference to a user advancing a needle and also provide a surface tosupport the needle connector and maintain alignment of the needle whenplaced.

The first extension 212 and the second extension 214 can be coupled tothe distal placement portion 220 in many ways. The extensions can becoupled to the distal portion so that pressing the extensions togetherseparates the first engagement structure 251 of the first side 222 fromthe second engagement structure 253 of the second side 224 as shown witharrows 228, for example (see FIGS. 3A and 3B). The extension 212 and theextension 214 can include springs such that the first engagementstructure 251 is urged toward the second engagement structure 253 whenthe user gently grasps the extensions without urging the extensionsinward. The first extension 212 on the first side 222 can extendtransverse to axis 200A and affix to second side 224, and the secondextension 214 can extend transverse to axis 200A and affix to first side222, for example. Alternatively, the first extension 212 and the secondextension 214 can be coupled to the distal placement portion 220 suchthat urging the extensions toward each other urges the first engagementstructure 251 toward the second engagement structure 253 so as to holdthe implantable device 100, and such that releasing the extensionsseparates the first engagement structure 251 from the second engagementstructure 253 with resilient spring force so as to release theimplantable device 100. The first extension 212 can extend and affix tofirst side 222 of the distal placement portion 220, and the secondextension 214 can extend and affix to second side 224, for example.

The first extension 212 and the second extension 214 can be affixed tothe distal placement portion 220 in many ways. Fasteners 226 can be usedto couple the extensions to the distal placement portion, for example.

FIGS. 3B and 3C show front and back views, respectively, of a distalplacement portion of the insertion apparatus of FIG. 3A. The firstengagement structure 251 includes a protrusion 262, and the secondengagement structure 253 includes a protrusion 264. The protrusion 262and the protrusion 264 are sized to fit in one or more recesses, such asthe narrow region, of the implantable device to retain the implantabledevice. The protrusion 262 includes a distal surface 256 to engage theshoulder of the implantable device, and the opposing protrusion 264includes a distal surface 258 to engage the implantable device on anopposite side. The projection 252 can include a flange 237, and theprojection 254 can include a support flange 239.

The first extension 212 can be affixed to the second side 224 of thedistal placement portion 220, and the second extension 214 can beaffixed to the first side 222 of the distal placement portion 220.

FIG. 3D and FIG. 3E show the implantable device 100 and the distalplacement portion 220 of the insertion apparatus 200 (FIG. 3A), theretention structure 120 (FIG. 2E) of the implantable device 100 can bealigned with the engagement structure 250 (FIG. 3A). The retentionstructure 120 includes a narrow portion 120N (FIG. 2E) dimensioned toreceive the protrusion 262 and the protrusion 264 (FIG. 3C) to hold theimplantable device. The protrusion 262 and the protrusion 264 (FIG. 3C)can be shaped in many ways to engage the narrow portion 120N (FIG. 2E),and can include lentoid, oval, elliptical or circular structures. Inmany embodiments, the protrusion 262 and the protrusion 264 (FIG. 3C)include a structure similar to the shape profile or outer contour of thenarrow portion 120N (FIG. 2E), and can include circular structures whenthe narrow portion 120N (FIG. 2E) includes a circular cross section, forexample. In many embodiments, the narrow portion 120N (FIG. 2E) includesone or more an oval, elliptical or lentoid geometry, and the protrusion262 and the protrusion 264 (FIG. 3C) include a corresponding geometry,for example.

The first protrusion 262 on first engagement structure 251 (FIG. 3C) caninclude a proximal surface 266 to engage a distal surface of theextension 122 of the retention structure 120 (FIG. 3D), and the secondprotrusion 264 on the second engagement structure 253 can include aproximal surface 268 to engage the distal surface of the extension 122of the retention structure 120, for example (FIG. 3C and FIG. 3D). Thefirst engagement structure 251 can be urged toward the second engagementstructure 253 to slide the first protrusion 262 and the secondprotrusion 264 (FIG. 3C) into the indentation 120N of the retentionstructure 120 (FIG. 2E).

FIGS. 3D and 3E show front and back views, respectively, of the distalplacement portion 220 of the insertion apparatus 200 (FIG. 3A) engagingthe implantable device 100. The first engagement structure 251 and thesecond engagement structure 253 extend substantially around theretention structure 120 (FIG. 2E) to hold the implantable device 100.FIG. 3D shows the extension 122 of the retention structure, as the restof the retention structure is obscured from view by the first and secondengagement structures, 251 and 253, respectively. FIG. 3E shows theshoulder 120S of the retention structure, as the rest of the retentionstructure is obscured from view by the first and second engagementstructures, 251 and 253, respectively. The implantable device 100 isheld such that the axis 100A of the implantable device is alignedsubstantially with the axis 200A of the insertion apparatus. Theimplantable device 100 can be held with the axis 100A substantiallyconcentric with the axis 200A of the insertion apparatus 200, forexample. FIG. 3D also shows elements of the distal placement portion 220shown in FIG. 3B and described herein above, such as the recess 231; theguide 230 that may have first and second proximal guide surfaces (232and 234, respectively), first and second intermediate guide surfaces(233 and 235, respectively), and first and second distal guide surfaces(236 and 238, respectively); and the support flanges 239 and 237. FIG.3E also shows the distal surfaces 256 and 258 of the engagementstructures 251 and 253, respectively.

FIG. 3F shows an injector 300 having a needle 310 advanced toward theimplantable device 100 held by the insertion apparatus 200. The injector300 can include needle 310 and a syringe 360, for example. The needle310 can be coupled to the syringe 360 with a connector 350. Theconnector 350 can include extensions 352 to couple the needle to thesyringe 360. The syringe 360 and the needle 310 may extend substantiallyalong an axis 300A. The needle 310 can include a housing 340. Thehousing 340 can include a plurality of structures to couple to or engagewith the guide 230, such that the needle 310 can be advanced along axis300A toward the proximal end of the implantable device 100. Theplurality of structures of the housing 340 can include a first structure320, a second structure 330, for example. The guide 230 and housing 340can be configured to align the axis 300A of the needle 310 oblique tothe axis 100A of the implantable device and the axis 200A of theinsertion apparatus when the needle 310 advances toward the penetrablebarrier of the implantable device 100. FIG. 3F also shows the recess231, the second projection 254, and the proximal surface 268 of theengagement structure.

FIG. 3G shows a side view of the implantable device 100 held with one ofthe engagement structures 251 and the needle 310 aligned obliquely withthe axis 100A of the implantable device. The protrusion 262 extendssubstantially into the narrow portion 120N of retention structure 120(FIG. 2E). The distal surface 256 of the protrusion 262 engages theshoulder 120S. The proximal surface 266 of the protrusion 262 of engagesthe distal surface of the extension 122 of the retention structure 120.The shoulder 120S can include a first shoulder 120S1 and a secondshoulder 120S2 on first and second sides, respectively, of the retentionstructure 120 as described herein, for example.

In many embodiments, the second engagement structure 253 includesstructure similar to the first engagement structure 251 as describedherein.

FIG. 3H shows the needle inserted obliquely into the implantable device100, for example to inject the therapeutic agent. The implantable devicecan include penetrable barrier 184 (FIG. 2E) having a first outersurface facing the syringe 360 and a second inner surface and athickness extending between the first surface and the second surface.The needle 310 can pass through the penetrable barrier 184 at an angleaway from perpendicular to the surfaces such that the needle 310 extendswithin the penetrable barrier 184 a distance greater than the thickness184D (shown in FIG. 2G). The housing 340 can be aligned substantiallywith the guide 230 so as to support the housing 340 with the guide 230when the needle 310 extends through the penetrable barrier 184. Forexample the surface 232 can be aligned substantially with the outersurface of the casing 340. A distal portion of the surface 233 can bealigned substantially with a distal portion of the structure 330. Adistal portion 322 of the structure 320 can engage the proximal surface266 so as to limit penetration of the needle 310 into the implantabledevice, for example.

FIG. 4A shows a removal tool 400. The removal tool 400 can include ahandle 410 and an engagement structure 450. The engagement structure 450can include a first engagement structure 451 and a second engagementstructure 453. The first engagement structure 451 can be located on afirst side of axis 400A, and the second engagement structure 453 can belocated on a second side of axis 400A opposite the first engagementstructure 451. The handle 410 can be configured in many ways and caninclude a first extension 412 and a second extension 414. The firstextension 412 and the second extension 414 may extend along oppositesides of an axis 400A. The extension 412 can be connected to theextension 414 at a proximal end 416. The extensions can be connected inmany ways, for example with weld. The extension 412 and the extension414 can include resilient material such that each extension includes acomponent of a spring. The first extension 412 can be urged toward thesecond extension 414 as shown with arrows 418, such that the firstengagement structure 451 is urged toward the second engagement structure453 as shown with arrows 428, for example. Alternatively, the engagementstructures can be connected to the extensions in many alternative waysas described herein, for example.

FIG. 4B shows the removal tool of FIG. 4A aligned with an implantabledevice 100. The conjunctiva and a Tenon's of the eye can be removed soas to expose device 100, which can be aligned with the removal tool 400as shown.

The first engagement structure 451 includes a first projection 452 and asecond projection 456 which extend toward axis 400A, so as to define achannel 482 sized to receive the indentation 120N of the implantabledevice 100. The first projection 452 includes a tapered portion 462extending to a leading edge 472. The second projection 456 includes atapered portion 466 extending to a leading edge 476. The leading edgesare configured to slide under the extension 122 of the retentionstructure 120.

The second engagement structure 453 includes a first projection 454 anda second projection 458 which extend toward axis 400A, so as to define achannel 484 sized to receive the indentation 120N of the implantabledevice 100. The first projection 454 includes a tapered portion 464extending to a leading edge 474. The second projection 458 includes atapered portion 468 extending to a leading edge 478. The leading edgesare configured to slide under the extension 122 of the retentionstructure 120 opposite the leading edges of the engagement structure451.

The axis 400A of the removal apparatus 400 can be aligned with the axis100A of the implantable device 100 when the engagement structures areurged toward each other.

FIGS. 4C and 4D show top and bottom views, respectively, of the removaltool 400 of FIGS. 4A and 4B holding the implantable device 100. Theleading edge 472, adjacent to tapered portion 462, engages the leadingedge 474, adjacent to tapered portion 464, so as to define a first stop,and the leading edge 476, adjacent to tapered portion 466, engages theleading edge 478, adjacent to tapered portion 468, so as to define asecond stop. The channel 482 and the channel 484 are sized to provide agap extending around the narrow portion 120N when leading edges ofengagement structure 451 engage the leading edges of the engagementstructure 453. The removal tool engages extension 122 of the retentionstructure 120 (FIG. 2E) with the proximal surfaces of projection 452,projection 454, projection 456 and projection 458, and the gap providesclearance to inhibit pinching of the narrow portion 120N of theretention structure. FIG. 4D also shows a shoulder 120S1 of theretention structure 120 in relation to the engagement structures 451 and453.

The retention structure 120 and the narrow portion 120N (FIG. 2A-G) ofthe retention structure can be configured in many ways as describedherein. In many embodiments, the long distance of the retentionstructure 120N is aligned such that the projections slide under theextension 122 in alignment with the long distance of the narrow portion120N. Alternatively, the short distance of the retention structure 120Nmay be aligned such that the projections slide under the extension 122in alignment with the short distance of the narrow portion 120N. Aperson of ordinary skill in the art will recognize many variations basedon the teachings and embodiments described herein, and the narrowportion 120N can include a substantially circular cross-sectional area,for example.

The removal tool 400 can be fabricated in many ways. For example,removal tool 400 can include a unitary structure. Alternatively, theextension and engagement structure of each side can include a unitarystructure fabricated from a single piece of material, and the twounitary structures can be joined together at the proximal end 416 forexample with a weld as described herein, for example.

FIG. 4E shows the removal tool 400 having opposing components 490holding a device with an alignment axis, 100A. The opposing components490 can include a first component 492 having first engagement structure451, and a second component 494 having second engagement structure 453.The first component 492 can be affixed to first extension 412 and thesecond component 494 can be affixed to the second extension 414, forexample.

FIGS. 5A to 5D show a method 500 of placing therapeutic device 100 in aneye 10.

FIG. 5A shows a step 510. At step 510, an injector apparatus 300 havinga needle is inserted into the implantable device 100 containing air 70.The device 100 is held by an insertion apparatus 200, and the injectorapparatus 300 fits into the guide 230 of the insertion apparatus 200.The insertion of the needle into the device 100 can be viewed through abinocular operating microscope 505. The needle can be inserted with theguide 230 into the recess as described herein when viewed throughmicroscope 505.

FIG. 5B shows a therapeutic fluid 119 having therapeutic agent 110placed in the implantable device 100 at a step 520. The therapeuticfluid can include a flowable material, for example a solution. The wallof the reservoir chamber of the therapeutic device 100 can include asubstantially transparent material so that the flow of the fluid 119toward the porous structure 150 on the distal end can be visualized.

FIG. 5C shows the therapeutic fluid injected such that some therapeuticfluid flows through a porous structure on the distal end of theimplantable device of FIG. 5A at a step 530. The therapeutic fluid 119,containing the therapeutic agent 110, can be injected through the porousstructure 150 so as to accumulate on the distal end of device 100. Theaccumulation of fluid 119 on the distal end can indicate to thephysician that the reservoir chamber of device 100 has been filled. Thephysician can inspect the device 100 for air bubbles, for example, so asto ensure the device has been filled properly.

FIG. 5D shows the implantable device 100 being placed in the eye 10 withinsertion apparatus 200 at a step 540. The device 100 filled withtherapeutic agent 110 can be implanted at the pars plana region 20 asdescribed herein. The conjunctiva can be removed from the sclera, andthe device 100 placed in the eye. The conjunctiva can be placed overdevice 100 and the conjunctiva sutured in place. Device 100 isconfigured such that a layer of Tenon's capsule can grow over theextension 122 of device 100 to retain device 100.

FIG. 6A shows a kit 600 having an insertion apparatus 200 and sterilepackaging 610. The kit 600 can include the insertion apparatus 200 andthe device 100 placed in the packaging. The retention structure of thedevice 100 can be mounted in the engagement structure of the apparatus200 as described herein when provided in the kit. Alternatively, thedevice 100 can be within sterile packaging 610 separated from apparatus200, and the device 100 engaged with apparatus 200 after the sterile kithas been opened, for example. The kit 600 can include the injectorapparatus 300.

FIG. 6B shows a kit 650 including a removal tool 400. The kit 650 caninclude sterile packaging 660 to protect removal apparatus 400.

While the exemplary embodiments have been described in some detail, byway of example and for clarity of understanding, those of skill in theart will recognize that a variety of modifications, adaptations, andchanges may be employed. Hence, the scope of the present disclosureshall be limited solely by the appended claims.

TABLE 1A Therapeutic Agent List Molecular Generic Name Brands(Companies) Category Indication Weight 2-Methoxyestradiol (PalomaAngiogenesis inhibitors AMD analogs Pharmaceuticals) 3-aminothalidomide13-cis retinoic acid Accutane TM (Roche Pharmaceuticals) A0003 (AqumenA0003 AMD BioPharmaceuticals) A5b1 integrin (Jerini Ophthalmic);Inhibitors of a5b1 AMD inhibitor (Ophthotech) integrin AbarelixPlenaxis ™ (Praecis Anti-Testosterone For palliative treatment 37731Pharmaceuticals) Agents; Antineoplastic of advanced prostate Agentscancer. Abatacept Orencia ™ (Bristol- Antirheumatic Agents For thesecond line 37697 Myers Squibb) reduction of the signs and symptoms ofmoderate-to-severe active rheumatoid arthritis, inducing major clinicalresponse, slowing the progression of structural damage, and improvingphysical function in adult patients who have Abciximab ReoPro ™;ReoPro ™ Anticoagulants; For treatment of 42632 (Centocor) AntiplateletAgents myocardial infarction, adjunct to percutaneous coronaryintervention, unstable angina ABT-578 (Abbott Laboratories) LimusImmunophilin Binding Compounds Acetonide Adalimumab Humira ™ (AbbottAntirheumatic Agents; Uveitis, AMD 25645 Laboratories) ImmunomodulatoryAgents Aldesleukin Proleukin ™; Antineoplastic Agents For treatment ofadults 61118 Proleukin ™ (Chiron with metastatic renal Corp) cellcarcinoma Alefacept Amevive ™ Immunomodulatory For treatment of 42632Agents; moderate to severe Immunosuppressive chronic plaque Agentspsoriasis Alemtuzumab Campath ™; Campath ™ Antineoplastic Agents Fortreatment of B-cell 6614 (ILEX Pharmaceuticals chronic lymphocytic LP);MabCampath ™ leukemia Alpha-1-proteinase Aralast ™ (Baxter); EnzymeReplacement For treatment of 28518 inhibitor Prolastin ™ (TalecrisAgents panacinar emphysema Biotherapeutics C formerly Bayer) AlteplaseActivase ™ (Genentech Thrombolytic Agents For management of 54732 Inc)acute myocardial infarction, acute ischemic stroke and for lysis ofacute pulmonary emboli AMG-1470 Anakinra Kineret ™ (Amgen Inc)Anti-Inflammatory For the treatment of 65403 Agents, Non-Steroidal;adult rheumatoid Antirheumatic Agents; arthritis. ImmunomodulatoryAgents Anecortave acetate Angiostatin Anistreplase Eminase ™ (WulfingThrombolytic Agents For lysis of acute 54732 Pharma GmbH) pulmonaryemboli, intracoronary emboli and management of myocardial infarctionAnti-angiogenesis (Eyecopharm) Anti-angiogenesis AMD peptides peptidesAnti-angiogenesis (TRACON Pharma) Anti-angiogenesis AMD antibodies,TRC093, antibodies TRC105 Anti-angiogeric Icon-1 ™ (IconicAnti-angiogeric AMD bifunctional protein Therapeutics) bifunctionalprotein, Icon-1 Anti-endothelial growth factor Antihemophilic Advate ™;Alphanate ™; Coagulants; Thrombotic For the treatment of 70037 FactorBioclate ™; Helixate ™; Agents hemophilia A, von Helixate FS ™; HemofilWillebrand disease and M ™; Humate-P ™; Factor XIII deficiencyHyate:C ™; Koate-HP ™; Kogenate ™; Kogenate FS ™; Monarc-M ™;Monoclate-P ™; ReFacto ™; Xyntha ™ Antithymocyte Genzyme);Immunomodulatory For prevention of renal 37173 globulin Thymoglobulin ™Agents transplant rejection (SangStat Medical Anti-hypertensive(MacuCLEAR) Anti-hypertensive AMD MC1101 MC1101 Anti-platelet deviredgrowth factor Anti-VEGF (Neurotech); Avastin ™ Anti-VEGF AMD (NeoVista)AP23841 (Ariad) Limus Immunophilin Binding Compounds ARC1905 OphthotechComplement Cascade Inhibitor (Factor C5) Aprotinin Trasylol ™Antifibrinolytic Agents For prophylactic use to 90569 reduceperioperative blood loss and the need for blood transfusion in patientsundergoing cardiopulmonary bypass in the course of coronary arterybypass graft surgery who are at an increased risk for blood loss andblood transfusion Arcitumomab CEA-Scan ™ Diagnostic Agents; For imagingcolorectal 57561 Imaging Agents tumors Asparaginase Elspar ™ (Merck &Co. Antineoplastic Agents For treatment of acute 132.118 Inc)lymphocytic leukemia and non-Hodgkins lymphoma Axitinib Tyrosine Kinase386 Inhibitors Basiliximab Simulect ™ (Novartis Immunomodulatory Forprophylactic 61118 Pharmaceuticals) Agents; treatment of kidneyImmunosuppressive transplant rejection Agents Becaplermin Regranex ™;Regranex ™ Anti-Ulcer Agents; For topical treatment 123969 (OMJPharmaceuticals) Topical of skin ulcers (from diabetes) BevacizumabAvastin ™; Avastin ™ Antiangiogenesis For treatment of 27043 (GenentechInc) Agents; Antineoplastic metastatic colorectal Agents cancerBivalirudin Angiomax ™; Anticoagulants; For treatment of 70037Angiomax ™ (Medicines Antithrombotic Agents heparin-induced Co or MDCO);thrombocytopenia Angiox ™ Bortezomib Proteosome Inhibitors BosutinibTyrosine Kinase 530 Inhibitors Botulinum Toxin BOTOX ™ (AllegranAnti-Wrinkle Agents; For the treatment of 23315 Type A Inc); BOTOXAntidystonic Agents; cervical dystonia in Cosmetic ™ (AllegranNeuromuscular Blocking adults to decrease the Inc); Botox ™; Agentsseverity of abnormal Dysport ™ head position and neck pain associatedwith cervical dystonia. Also for the treatment of severe primaryaxillary hyperhidrosis that is inadequately managed with topicalBotulinum Toxin Myobloc ™ (Solstice Antidystonic Agents For thetreatment of 12902 Type B Neurosciences); patients with cervicalNeurobloc ™ (Solstice dystonia to reduce the Neurosciences) severity ofabnormal head position and neck pain associated with cervical dystonia.C5 inhibitor (Jerini Ophthalmic); Inhibitors of C5 AMD (Ophthotech)Cal101 Calistoga PI3Kdelta Inhibitor AMD, DME Canstatin CapromabProstaScint ™ (Cytogen Imaging Agents For diagnosis of 84331 Corp)prostate cancer and detection of intra- pelvic metastases Captopril ACEInhibitors CCI-779 (Wyeth) Limus Immunophilin Binding CompoundsCediranib Tyrosine Kinase 450 Inhibitors Celecoxib CyclooxygenaseInhibitors Cetrorelix Cetrotide ™ Hormone Antagonists; For theinhibition of 78617 Infertility Agents premature LH surges in womenundergoing controlled ovarian stimulation Cetuximab Erbitux ™; Erbitux ™Antineoplastic Agents For treatment of 42632 (ImClone Systems Inc)metastatic colorectal cancer. Choriogonadotropin Novarel ™; Ovidrel ™;Fertility Agents; For the treatment of 78617 alfa Pregnyl ™; Profasi ™Gonadotropins female infertility Cilary neurotrophic (Neurotech) Ciliaryneurotrophic AMD factor factor Coagulation Factor Benefix ™ (GeneticsCoagulants; Thrombotic For treatment of 267012 IX Institute) Agentshemophilia (Christmas disease). Coagulation factor NovoSeven ™ (NovoCoagulants; Thrombotic For treatment of 54732 VIIa Nordisk) Agentshemorrhagic complications in hemophilia A and B Colchicines CollagenaseCordase ™; Santyl ™ Anti-Ulcer Agents; For treatment of 138885 (AdvanceBiofactures Topical chronic dermal ulcers Corp); Xiaflextm ™ and severeskin burns Complement factor H (Optherion); (Taligen Complement factor HAMD, Geographic recombinant Therapeutics) recombinant Atrophy Compstatinderivative (Potentia Complement Factor C3 AMD peptide, POT-4Pharmaceuticals) Inhibitors; Compstatin Derivative PeptidesCorticotropin ACTH ™; Acethropan ™; Diagnostic Agents For use as adiagnostic 33927 Acortan ™; Acthar ™; agent in the screening Exacthin ™;H.P. Acthar of patients presumed to Gel ™; Isactid ™; haveadrenocortical Purified cortrophin insufficiency. gel ™; Reacthin ™;Solacthyl ™; Tubex Cosyntropin Cortrosyn ™; Synacthen Diagnostic AgentsFor use as a diagnostic 33927 depot ™ agent in the screening of patientspresumed to have adrenocortical insufficiency. Cyclophilins LimusImmunophilin Binding Compounds Cyclosporine Gengraf ™ (Abbott labs);Antifungal Agents; For treatment of 32953 Neoral ™ (Novartis);Antirheumatic Agents; transplant rejection, Restasis ™; Restasis ™Dermatologic Agents; rheumatoid arthritis, (Allergan Inc); EnzymeInhibitors; severe psoriasis Sandimmune ™ Immunomodulatory (Novartis);Sangcya ™ Agents; Immunosuppressive Agents Daclizumab Zenapax ™(Hoffmann- Immunomodulatory For prevention of renal 61118 La Roche Inc)Agents; transplant rejection; Immunosuppressive Uveitis AgentsDarbepoetin alfa Aranesp ™ (Amgen Inc.) Antianemic Agents For thetreatment of 55066 anemia (from renal transplants or certain HIVtreatment) Dasatinib Tyrosine Kinase 488 Inhibitors DefibrotideDasovas ™; Noravid ™; Antithrombotic Agents Defibrotide is used to 36512Prociclide ™ treat or prevent a failure of normal blood flow (occlusivevenous disease, OVD) in the liver of patients who have had bone marrowtransplants or received certain drugs such as oral estrogens,mercaptopurine, and many others. Denileukin diftitox Ontak ™Antineoplastic Agents For treatment of 61118 cutaneous T-cell lymphomaDesmopressin Adiuretin ™; Antidiuretic Agents; For the management of46800 Concentraid ™; Hemostatics; Renal primary nocturnal Stimate ™Agents enuresis and indicated as antidiuretic replacement therapy in themanagement of central diabetes insipidus and for the management of thetemporary polyuria and polydipsia following head trauma or surgery inthe pitu Dexamethasone Ozurdex ™ (Allergan) Glucocorticoid DME,inflammation, 392 macular edema following branch retinal vein occlusion(BRVO) or central retinal vein occlusion (CRVO) DiclofenacCyclooxygenase Inhibitors Dithiocarbamate NFκB Inhibitor Dornase AlfaDilor ™; Dilor-400 ™; Enzyme Replacement For the treatment of 7656Lufyllin ™; Lufyllin- Agents cystic fibrosis. (double 400 ™;Neothylline ™; strand) Pulmozyme ™ (Genentech Inc) Drotrecogin alfaXigris ™; Xigris ™ (Eli Antisepsis Agents For treatment of severe 267012Lilly & Co) sepsis Eculizumab Soliris ™; Soliris ™ Complement CascadeAMD 188333 (Alexion Inhibitor (Factor C5) Pharmaceuticals) EfalizumabRaptiva ™; Raptiva ™ Immunomodulatory For the treatment of 128771(Genentech Inc) Agents; adult patients with Immunosuppressive moderateto severe Agents chronic plaque psoriasis, who are candidates forphototherapy or systemic therapy. Endostatin Enfuvirtide Fuzeon ™;Fuzeon ™ Anti-HIV Agents; HIV For treatment of HIV 16768 (RochePharmaceuticals) Fusion Inhibitors AIDS Epoetin alfa Epogen ™ (AmgenInc.); Antianemic Agents For treatment of 55066 Epogin ™ (Chugai);anemia (from renal Epomax ™ (Elanex); transplants or certain Eprex ™(Janssen-Cilag. HIV treatment) Ortho Biologics LLC); NeoRecormon ™(Roche); Procrit ™ (Ortho Biotech); Recormon ™ (Roche) EptifibatideIntegrilin ™; Integrilin ™ Anticoagulants; For treatment of 7128(Millennium Pharm) Antiplatelet Agents; myocardial infarction PlateletAggregation and acute coronary Inhibitors syndrome. Erlotinib TyrosineKinase 393 Inhibitors Etanercept Enbrel ™; Enbrel ™ AntirheumaticAgents; Uveitis, AMD 25645 (Immunex Corp) Immunomodulatory AgentsEverolimus Novartis Limus Immunophilin AMD Binding Compounds, mTORExenatide Byetta ™; Byetta ™ Indicated as adjunctive 53060 (Amylin/EliLilly) therapy to improve glycemic control in patients with Type 2diabetes mellitus who are taking metformin, a sulfonylurea, or acombination of both, but have not achieved adequate glycemic control.FCFD4514S Genentech/Roche Complement Cascade AMD, Geographic Inhibitor(Factor D) Atrophy Felypressin Felipresina ™ [INN- Renal Agents; For useas an 46800 Spanish]; Felipressina ™ Vasoconstrictor Agents alternativeto [DCIT]; Felypressin ™ adrenaline as a [USAN:BAN:INN]; localizingagent, Felypressine ™ [INN- provided that local French]; ischaemia isnot Felypressinum ™ [INN- essential. Latin]; Octapressin ™ FenretinideSirion/reVision Binding Protein AMD, Geographic Therapeutics Antagonistfor Oral Atrophy Vitamin A Filgrastim Neupogen ™ (Amgen Anti-InfectiveAgents; Increases leukocyte 28518 Inc.) Antineutropenic Agents;production, for Immunomodulatory treatment in non- Agents myeloidcancer, neutropenia and bone marrow transplant FK605-binding LimusImmunophilin proteins, FKBPs Binding Compounds Fluocinolone Retisert ™(Bausch & Glucocorticoid Retinal inflammation, 453 Acetonide Lomb);Iluvien ™ diabetic macular (Alimera Sciences, Inc.) edema Follitropinbeta Follistim ™ (Organon); Fertility Agents For treatment of 78296Gonal F ™; Gonal-F ™ female infertility Fumagillin GalsulfaseNaglazyme ™; Enzyme Replacement For the treatment of 47047 Naglazyme ™(BioMarin Agents adults and children Pharmaceuticals) withMucopolysaccharidosis VI. Gefitinib Tyrosine Kinase 447 InhibitorsGemtuzumab Mylotarg ™; Mylotarg ™ Antineoplastic Agents For treatment ofacute 39826 ozogamicin (Wyeth) myeloid leukemia Glatiramer AcetateCopaxone ™ Adjuvants, For reduction of the 29914 Immunologic; frequencyof relapses Immunosuppressive in patients with AgentsRelapsing-Remitting Multiple Sclerosis. Glucagon GlucaGen ™ (NovoAntihypoglycemic For treatment of severe 54009 recombinant Nordisk);Glucagon ™ Agents hypoglycemia, also (Eli Lilly) used ingastrointestinal imaging Goserelin Zoladex ™ Antineoplastic Agents;Breast cancer; Prostate 78617 Antineoplastic Agents, carcinoma; HormonalEndometriosis Human Serum Albutein ™ (Alpha Serum substitutes Fortreatment of severe 39000 Albumin Therapeutic Corp) blood loss,hypervolemia, hypoproteinemia Hyaluronidase Vitragan ™; Vitrase ™;Anesthetic Adjuvants; For increase of 69367 Vitrase ™ (Ista Pharma)Permeabilizing Agents absorption and distribution of other injecteddrugs and for rehydration Ibritumomab Zevalin ™ (IDEC AntineoplasticAgents For treatment of non- 33078 Pharmaceuticals) Hodgkin's lymphomaIdursulfase Elaprase ™ (Shire Enzyme Replacement For the treatment of47047 Pharmaceuticals) Agents Hunter syndrome in adults and childrenages 5 and older. Imatinib Tyrosine Kinase AMD, DME 494 InhibitorsImmune globulin Civacir ™; Anti-Infectives; For treatment of 42632Flebogamma ™ (Instituto Immunomodulatory immunodeficiencies, GrifolsSA); Gamunex ™ Agents thrombocytopenic (Talecris purpura, KawasakiBiotherapeutics) disease, gammablobulinemia, leukemia, bone transplantInfliximab Remicade ™ (Centocor Immunomodulatory Uveitis, AMD 25645 Inc)Agents; Immunosuppressive Agents Insulin Glargine Lantus ™ HypoglycemicAgents For treatment of 156308 recombinant diabetes (type I and II)Insulin Lyspro Humalog ™ (Eli Lily); Hypoglycemic Agents For treatmentof 154795 recombinant Insulin Lispro (Eli Lily) diabetes (type I and II)Insulin recombinant Novolin R ™ (Novo Hypoglycemic Agents For treatmentof 156308 Nordisk) diabetes (type I and II) Insulin, porcine Iletin II ™Hypoglycemic Agents For the treatment of 156308 diabetes (type I and II)Interferon Interferon Alfa-2a, Roferon A ™ Antineoplastic Agents; Fortreatment of 57759 Recombinant (Hoffmann-La Roche Antiviral Agentschronic hepatitis C, Inc); Veldona ™ hairy cell leukemia, (AmarilloBiosciences) AIDS-related Kaposi's sarcoma, and chronic myelogenousleukemia. Also for the treatment of oral warts arising from HIVinfection. Interferon Alfa-2b, Intron A ™ (Schering AntineoplasticAgents; For the treatment of 57759 Recombinant Corp) Antiviral Agents;hairy cell leukemia, Immunomodulatory malignant melanoma, Agents andAIDS-related Kaposi's sarcoma. Interferon alfacon-1 Advaferon ™;Infergen ™ Antineoplastic Agents; For treatment of hairy 57759(InterMune Inc) Antiviral Agents; cell leukemia, Immunomodulatorymalignant melanoma, Agents and AIDS-related Kaposi's sarcoma Interferonalfa-n1 Wellferon ™ Antiviral Agents; For treatment of 57759(GlaxoSmithKline) Immunomodulatory venereal or genital Agents wartscaused by the Human Papilloma Virus Interferon alfa-n3 Alferon ™(Interferon Antineoplastic Agents; For the intralesional 57759 SciencesInc.); Alferon Antiviral Agents; treatment of refractory LDO ™; AlferonN Immunomodulatory or recurring external Injection ™ Agents condylomatacuminate. Interferon beta-1b Betaseron ™ (Chiron Antiviral Agents; Fortreatment of 57759 Corp) Immunomodulatory relapsing/remitting Agentsmultiple sclerosis Interferon gamma-1b Actimmune ™; Antiviral Agents;For treatment of 37835 Actimmune ™ Immunomodulatory Chronicgranulomatous (InterMune Inc) Agents disease, Osteopetrosis LapatinibTyrosine Kinase 581 Inhibitors Lepirudin Refludan ™ Anticoagulants; Forthe treatment of 70037 Antithrombotic Agents; heparin-inducedFibrinolytic Agents thrombocytopenia Lestaurtinib Tyrosine Kinase 439Inhibitors Leuprolide Eligard ™ (Atrix Anti-Estrogen Agents; Fortreatment of 37731 Labs/QLT Inc) Antineoplastic Agents prostate cancer,endometriosis, uterine fibroids and premature puberty Lutropin alfaLuveris ™ (Serono) Fertility Agents For treatment of 78617 femaleinfertility Mecasermin Increlex ™; Increlex ™ For the long-term 154795(Tercica); Iplex treatment of growth failure in pediatric patients withPrimary IGFD or with GH gene deletion who have developed neutralizingantibodies to GH. It is not indicated to treat Secondary IGFD resultingfrom GH deficiency, malnutrition, hypoth Menotropins Repronex ™Fertility Agents For treatment of 78617 female infertility MethotrexateImmunomodulatory Uveitis, DME mTOR inhibitors Muromonab OrthocloneOKT3 ™ Immunomodulatory For treatment of organ 23148 (Ortho Biotech)Agents; transplant recipients, Immunosuppressive prevention of organAgents rejection Natalizumab Tysabri ™ Immunomodulatory For treatment of115334 Agents multiple sclerosis. Nepafenac Cyclooxygenase InhibitorsNesiritide Natrecor ™ Cardiac drugs For the intravenous 118921 treatmentof patients with acutely decompensated congestive heart failure who havedyspnea at rest or with minimal activity. Nilotinib Tyrosine Kinase 530Inhibitors NS398 Cyclooxygenase Inhibitors Octreotide Atrigel ™;Anabolic Agents; For treatment of 42687 Longastatin ™; AntineoplasticAgents, acromegaly and Sandostatin ™; Hormonal; reduction of sideSandostatin LAR ™; Gastrointestinal Agents; effects from cancerSandostatin LAR ™ Hormone Replacement chemotherapy (Novartis) AgentsOmalizumab Xolair ™ (Genentech Anti-Asthmatic Agents; For treatment of29596 Inc) Immunomodulatory asthma caused by Agents allergies OprelvekinNeumega ™; Neumega ™ Coagulants; Thrombotics Increases reduced 45223(Genetics Institute Inc) platelet levels due to chemotherapy OspAlipoprotein LYMErix ™ (SmithKline Vaccines For prophylactic 95348Beecham) treatment of Lyme Disease OT-551 (Othera) Anti-oxidant eyedropAMD Oxytocin Oxytocin ™ (BAM Anti-tocolytic Agents; To assist in labor,12722 Biotech); Pitocin ™ Labor Induction Agents; elective labor(Parke-Davis); Oxytocics induction, uterine Syntocinon ™ (Sandoz)contraction induction Palifermin Kepivance ™ (Amgen Antimucositis AgentsFor treatment of 138885 Inc) mucositis (mouth sores) PalivizumabSynagis ™ Antiviral Agents For treatment of 63689 respiratory diseasescasued by respiratory syncytial virus Panitumumab Vectibix ™; Vectibix ™Antineoplastic Agents For the treatment of 134279 (Amgen)EGFR-expressing, metastatic colorectal carcinoma with diseaseprogression on or following fluoropyrimidine-, oxaliplatin-, andirinotecan-containing chemotherapy regimens. PDGF inhibitor (JeriniOphthalmic); Inhibitors of PDGF AMD (Ophthotech) PEDF (pigmentepithelium derived factor) Pegademase bovine Adagen ™ (Enzon Inc.)Enzyme Replacement For treatment of 36512 Agents adenosine deaminasedeficiency Pegaptanib Macugen ™ Oligonucleotide For the treatment of103121 neovascular (wet) age- related macular degeneration. PegaspargaseOncaspar ™ (Enzon Inc) Antineoplastic Agents For treatment of acute132.118 lymphoblastic leukemia Pegfilgrastim Neulasta ™ (Amgen Inc.)Anti-Infective Agents; Increases leukocyte 28518 Antineutropenic Agents;production, for Immunomodulatory treatment in non- Agents myeloidcancer, neutropenia and bone marrow transplant Peginterferon alfa-2aPegasys ™ (Hoffman-La Antineoplastic Agents; For treatment of hairy57759 Roche Inc) Antiviral Agents; cell leukemia, Immunomodulatorymalignant melanoma, Agents and AIDS-related Kaposi's sarcoma.Peginterferon alfa-2b PEG-Intron (Schering Antineoplastic Agents; Forthe treatment of 57759 Corp); Unitron PEG ™ Antiviral Agents; chronichepatitis C in Immunomodulatory patients not previously Agents treatedwith interferon alpha who have compensated liver disease and are atleast 18 years of age. Pegvisomant Somavert ™ (Pfizer Inc) AnabolicAgents; For treatment of 71500 Hormone Replacement acromegaly AgentsPentoxifylline Perindozril ACE Inhibitors Pimecrolimus LimusImmunophilin Binding Compounds PKC (protein kinase C) inhibitors POT-4Potentia/Alcon Complement Cascade AMD Inhibitor (Factor C3) PramlintideSymlin ™; Symlin ™ For the mealtime 16988 (Amylin treatment of Type Iand Pharmaceuticals) Type II diabetes in combination with standardinsulin therapy, in patients who have failed to achieve adequate glucosecontrol on insulin monotherapy. Proteosome inhibitors Velcade ™Proteosome inhibitors Pyrrolidine Quinopril ACE Inhibitors RanibizumabLucentis ™ For the treatment of 27043 patients with neovascular (wet)age- related macular degeneration. Rapamycin (MacuSight) LimusImmunophilin AMD (siroliums) Binding Compounds Rasburicase Elitek ™;Elitek ™ Antihyperuricemic For treatment of 168.11 (Sanofi-SynthelaboInc); Agents hyperuricemia, reduces Fasturtec ™ elevated plasma uricacid levels (from chemotherapy) Reteplase Retavase ™ (Centocor);Thrombolytic Agents For lysis of acute 54732 Retavase ™ (Roche)pulmonary emboli, intracoronary emboli and management of myocardialinfarction Retinal stimulant Neurosolve ™ Retinal stimulants AMD(Vitreoretinal Technologies) Retinoid(s) Rituximab MabThera ™; Rituxan ™Antineoplastic Agents For treatment of B-cell 33078 non-Hodgkinslymphoma (CD20 positive) RNAI (RNA interference of angiogenic factors)Rofecoxib Vioxx ™; Ceoxx ™; Cyclooxygenase Ceeoxx ™ (Merck & InhibitorsCo.) Rosiglitazone Thiazolidinediones Ruboxistaurin Eli Lilly ProteinKinase C (PKC)- DME, diabetic 469 b Inhibitor peripheral retinopathySalmon Calcitonin Calcimar ™; Miacalcin ™ Antihypocalcemic For thetreatment of 57304 (Novartis) Agents; Antiosteporotic post-menopausalAgents; Bone Density osteoporosis Conservation Agents SargramostimImmunex ™; Anti-Infective Agents; For the treatment of 46207 Leucomax ™(Novartis); Antineoplastic Agents; cancer and bone Leukine ™; Leukine ™Immunomodulatory marrow transplant (Berlex Laboratories Inc) Agents SAR1118 SARCode Immunomodulatory Dry eye, DME, Agent conjunctivitis SDZ-RADLimus Immunophilin Binding Compounds Secretin SecreFlo ™; DiagnosticAgents For diagnosis of 50207 Secremax ™, SecreFlo ™ pancreatic exocrine(Repligen Corp) dysfunction and gastrinoma Selective inhibitor of thefactor 3 complement cascade Selective inhibitor of the factor 5complement cascade Semaxanib Tyrosine Kinase 238 Inhibitors SermorelinGeref ™ (Serono Anabolic Agents; For the treatment of 47402 Pharma)Hormone Replacement dwarfism, prevention Agents of HIV-induced weightloss Serum albumin Megatope ™ (IsoTex Imaging Agents For determinationof 39000 iodinated Diagnostics) total blood and plasma volumes SF1126Semafore PI3k/mTOR Inhibition AMD, DME Sirolimus (MacuSight) LimusImmunophilin AMD reformulation Binding Compounds (rapamycin) siRNAmolecule (Quark siRNA molecule AMD synthetic, FTP-801i- Pharmaceuticals)synthetic 14 Somatropin BioTropin ™ (Biotech Anabolic Agents; Fortreatment of 71500 recombinant General); Genotropin ™ HormoneReplacement dwarfism, acromegaly (Pfizer); Humatrope ™ Agents andprevention of HIV- (Eli Lilly); induced weight loss Norditropin ™ (NovoNordisk); Nutropin ™ (Genentech Inc.); NutropinAQ ™ (Genentech Inc.);Protropin ™ (Genentech Inc.); Saizen ™ (Serono SA); Serostim ™;Serostim ™ (Serono SA); Tev-Tropin ™ (GATE) Squalamine StreptokinaseStreptase ™ (Aventis Thrombolytic Agents For the treatment of 90569Behringer GmbH) acute evolving transmural myocardial infarction,pulmonary embolism, deep vein thrombosis, arterial thrombosis orembolism and occlusion of arteriovenous cannulae Sunitinib TyrosineKinase 398 Inhibitors TA106 Taligen Complement Cascade AMD Inhibitor(Factor B) Tacrolimus Limus Immunophilin Binding Compounds TenecteplaseTNKase ™ (Genentech Thrombolytic Agents For treatment of 54732 Inc)myocardial infarction and lysis of intracoronary emboli TeriparatideApthela ™; Forsteo ™; Bone Density For the treatment of 66361 Forteo ™;Fortessa ™; Conservation Agents osteoporosis in men Opthia ™; Optia ™;and postmenopausal Optiah ™; Zalectra ™; women who are at highZelletra ™ risk for having a fracture. Also used to increase bone massin men with primary or hypogonadal osteoporosis who are at high risk forfracture. Tetrathiomolybdate Thalidomide Celgene Anti-inflammatory,Anti- Uveitis proliferative Thyrotropin Alfa Thyrogen ™ (GenzymeDiagnostic Agents For detection of 86831 Inc) residual or recurrentthyroid cancer Tie-1 and Tie-2 kinase inhibitors Toceranib TyrosineKinase 396 Inhibitors Tositumomab Bexxar ™ (Corixa Corp) AntineoplasticAgents For treatment of non- 33078 Hodgkin's lymphoma (CD20 positive,follicular) TPN 470 analogue Trastuzumab Herceptin ™ (Genentech)Antineoplastic Agents For treatment of 137912 HER2-positive pulmonarybreast cancer Triamcinolone Triesence ™ Glucocorticoid DME, Fortreatment of 435 acetonide inflammation of the retina TroglitazoneThiazolidinediones Tumistatin Urofollitropin Fertinex ™ (Serono S.A.)Fertility Agents For treatment of 78296 female infertility UrokinaseAbbokinase ™; Thrombolytic Agents For the treatment of 90569Abbokinase ™ (Abbott pulmonary embolism, Laboratories) coronary arterythrombosis and IV catheter clearance Vandetanib Tyrosine Kinase 475Inhibitors Vasopressin Pitressin ™; Pressyn ™ Antidiuretics; Oxytocics;For the treatment of 46800 Vasoconstrictor Agents enuresis, polyuria,diabetes insipidus, polydipsia and oesophageal varices with bleedingVatalanib Tyrosine Kinase 347 Inhibitors VEGF receptor kinase inhibitorVEGF Trap Aflibercept ™ (Regneron Genetically Engineered DME, cancer,retinal 96600 Pharmaceuticals, Bayer Antibodies vein occlusion,HealthCare AG) choroidal neovascularization, delay wound healing, cancertreatment Visual Cycle (Acucela) Visual Cycle Modulator AMD ModulatorACU- 4229 Vitamin(s) Vitronectin receptor antagonists VolociximabOphthotech alpha5beta1 Integrin AMD Inhibitor XL765Exelixis/Sanofi-Aventis PI3k/mTOR Inhibition AMD, DME

1. An apparatus to insert an implantable therapeutic device into apatient, the apparatus comprising: a proximal handle; and a distalplacement portion coupled to the proximal handle and configured to holdthe implantable therapeutic device, the distal placement portioncomprising: a first side having a first engagement structure at a distalend of the first side, the first engagement structure configured tosurround at least a first portion of a proximal end region of theimplantable therapeutic device; and a second, opposite side having asecond engagement structure at a distal end of the second side, thesecond engagement structure configured to surround at least a second,opposite portion of the proximal end region of the implantabletherapeutic device.
 2. The apparatus of claim 1, further comprising theimplantable therapeutic device, wherein the implantable therapeuticdevice includes a retention structure at the proximal end regioncomprising a narrow portion, a shoulder and a proximal extension.
 3. Theapparatus of claim 2, wherein each of the first and second engagementstructures includes a protrusion having a surface contour shaped andsized to engage a portion of the retention structure.
 4. The apparatusof claim 3, wherein each of the protrusions is configured to extend intothe narrow portion.
 5. The apparatus of claim 4, wherein when theprotrusions extend into the narrow portion, a proximal surface of eachprotrusion engages a distal surface of the proximal extension and adistal surface of each protrusion engages the shoulder.
 6. The apparatusof claim 2, wherein the distal placement portion further comprises arecess through which a proximal surface of the proximal extension isaccessible.
 7. The apparatus of claim 6, wherein the distal placementportion further comprises a guide having at least one guide surfaceconfigured to support and maintain alignment of a needle extending at anangle oblique to a longitudinal axis of the implantable device prior topenetration of the implantable device by the needle.
 8. The apparatus ofclaim 7, wherein the needle includes a connector and wherein the atleast one guide surface has a shape complimentary to the connector toreceive the connector and maintain alignment of the needle relative tothe implantable device.
 9. The apparatus of claim 1, wherein theproximal handle includes first and second opposing handles extending onopposite sides of a longitudinal axis, wherein the first opposing handleis coupled to a proximal end of the first side and the second opposinghandle is coupled to a proximal end of the second side.
 10. Theapparatus of claim 9, wherein the first and second opposing handles areconfigured to urge the first side and the second side toward each otherto engage the implantable device when the first and second opposinghandles move away from the axis and to urge the first side and thesecond side away from each other to release the implantable device whenthe first and second opposing handles move toward the axis.
 11. Theapparatus of claim 9, wherein the first and second opposing handles areconfigured to urge the first side and the second side toward each otherto engage the implantable device when the first and second opposinghandles move toward the axis and to urge the first side and the secondside away from each other to release the implantable device when thefirst and second opposing handles move away from the axis.
 12. A methodof treating a patient, the method comprising: holding with an insertionapparatus an implantable device comprising an axis and a penetrablebarrier, such that the axis of the implantable device and an axis of theinsertion apparatus are concentric; advancing a needle through thepenetrable barrier at an angle oblique to the concentric axes; injectinga therapeutic fluid through the needle advanced through the penetrablebarrier and into a reservoir chamber of the implantable device; andimplanting the implantable device into an incision in a tissue of thepatient.
 13. The method of claim 12, wherein the axis of the implantabledevice and the axis of the insertion apparatus are concentric when thetherapeutic fluid is injected into the reservoir chamber of theimplantable device.
 14. The method of claim 13, wherein the insertionapparatus includes the apparatus of claim
 1. 15. A kit to treat apatient, the kit comprising: an insertion apparatus of claim 1; animplantable therapeutic device; and packaging to contain the insertionapparatus and the implantable therapeutic device.